Primary care supply and quality of care in England.
We investigated the relationship between primary care supply and quality of care in England. We analysed 35 process measures of quality of care covering 13 medical conditions using English Longitudinal Study of Aging data linked to area of residence indicators. Greater GP density had a statistically significant and positive association with quality of care, and distance to GP practice had a statistically significant and negative association. The effects were concentrated in indicators of care related to cardiovascular diseases and arthritis, and on specific indicators for diabetes, incontinence and hearing problems. The results suggest that better primary care supply can improve quality of care.


Red wine inhibits the cell-mediated oxidation of LDL and HDL.
We compared the in vitro effects of red wine, white wine and ethanol on the cell mediated oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) by three frequently-used assays. LDL and HDL isolated from normolipidemic human serum were incubated with J774.A1 macrophages in DMEM with copper, with or without red wine, white wine or ethanol (equivalent to 0.2 mg ethanol/ml). Lipoprotein oxidation was assessed by conjugated diene formation as measured by changes in absorbance at 234 nm (deltaA234), thiobarbituric-acid-reactive-substance (TBARS) production and trinitrobenzene-sulfonic-acid (TNBS) reactivity. Red wine (0.2 mg ethanol/mL) inhibited LDL oxidation as indicated by an 85.7% decrease in absorbance at 234 nm, a 96.5% decrease in TBARS production and complete prevention of the decrease in TNBS reactivity. White wine and ethanol did not have any significant effect at 0.2 mg/mL. White wine at 1.0 mg ethanol/mL inhibited TBARS production from LDL by 84.1%. Red wine (0.2 mg ethanol/mL) inhibited HDL oxidation as indicated by a 78.9% decrease in deltaA234, an 81.7% decrease in TBARS production and by no change in TNBS reactivity. White wine and ethanol had no effect at 0.2 mg/mL. White wine at 1.0 mg ethanol/mL inhibited TBARS production from HDL by 66.4%. These results indicate that red wine inhibits the cell mediated oxidation of lipoproteins, that white wine is not as effective as red wine and that the effect of the red wine is not due to its ethanol content.


Internet of things security evaluation mechanism based on meta attribute fluctuation.
In the field of Internet of Things (IoT), terminal security has always been an extremely important independent research topic. In the terminal security research, in addition to the security enhancement of terminal entities, the security status evaluation of terminal security has also become an independent subset of the security research in the IoT field. However, it should also be noted that the security attributes of IoT terminals can include many aspects, so judging the security of IoT terminals based on the overall security form is not enough for the security of terminal entities. This paper introduces the concept of volatility from the overall situation assessment to the meta attributes that constitute the overall security situation, and preliminarily realizes the construction of a concise model based on historical data to judge the meta attributes that may affect the overall security in the future. At the same time, a concise verification system is built based on the application scenario of the power IoT terminals currently under research to preliminarily realize trend prediction, further expand the trust evaluation of IoT terminals, and clarify the direction of further research.


A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B.
Background: Evidence from randomized controlled trials (RCTs) suggests the consumption of konjac glucomannan (KJM), a viscous soluble fiber, for improving LDL-cholesterol concentrations. It has also been suggested that the cholesterol-lowering potential of KJM may be greater than that of other fibers. However, trials have been relatively scarce and limited in sample size and duration, and the effect estimates have been inconsistent. The effect of KJM on new lipid targets of cardiovascular disease (CVD) risk is also unknown.Objective: This systematic review and meta-analysis aimed to assess the effect of KJM on LDL cholesterol, non-HDL cholesterol, and apolipoprotein B.Design: Medline, Embase, CINAHL, and the Cochrane Central databases were searched. We included RCTs with a follow-up of ≥3 wk that assessed the effect of KJM on LDL cholesterol, non-HDL cholesterol, or apolipoprotein B. Data were pooled by using the generic inverse-variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I2 statistic.Results: Twelve studies (n = 370), 8 in adults and 4 in children, met the inclusion criteria. KJM significantly lowered LDL cholesterol (MD: -0.35 mmol/L; 95% CI: -0.46, -0.25 mmol/L) and non-HDL cholesterol (MD: -0.32 mmol/L; 95% CI: -0.46, -0.19 mmol/L). Data from 6 trials suggested no impact of KJM on apolipoprotein B.Conclusions: Our findings support the intake of ∼3 g KJM/d for reductions in LDL cholesterol and non-HDL cholesterol of 10% and 7%, respectively. The information may be of interest to health agencies in crafting future dietary recommendations related to reduction in CVD risk. This study was registered at clinicaltrials.gov as NCT02068248.


Near-Field Beamforming Algorithms for UAVs.
This study presents three distributed beamforming algorithms to address the challenges of positioning and signal phase errors in unmanned aerial vehicle (UAV) arrays that hinder effective beamforming. Firstly, the array's received signal phase error model was analyzed under near-field conditions. In the absence of navigation data, a beamforming algorithm based on the Extended Kalman Filter (EKF) was proposed. In cases where navigation data were available, Taylor expansion was utilized to simplify the model, the non-Gaussian noise of the compensated received signal phase was approximated to Gaussian noise, and the noise covariance matrix in the Kalman Filter (KF) was estimated. Then, a beamforming algorithm based on KF was developed. To further estimate the Gaussian noise distribution of the received signal phase, the noise covariance matrix was iteratively estimated using unscented transformation (UT), and here, a beamforming algorithm based on the Unscented Kalman Filter (UKF) was proposed. The proposed algorithms were validated through simulations, illustrating their ability to suppress the malign effects of errors on near-field UAV array beamforming. This study provides a reference for the implementation of UAV array beamforming under varying conditions.


[Effect of low-molecular heparin on blood coagulation].
The coagulation-inhibiting effect of subcutaneously administered commercial and a low-molecular heparin was compared in healthy volunteers. Global clotting activity, measured as activated partial thromboplastin time as well as thrombin activity were inhibited almost equally by commercial and low-molecular heparin. Low-molecular heparin caused a ten-fold stronger inhibition of factor Xa. The effect on factor Xa increased nearly logarithmically with the injected dose. Half-life of heparin measured in terms of the inhibition of factor Xa was 5.5 hours for the low-molecular and 3.5 hours for the commercial preparation. These results indicate that low-molecular heparin has a high specificity in the inhibition of factor Xa. A lower dose of low-molecular heparin, administered once daily, may have an anti-thrombotic effect while reducing the risk of bleeding.


First-principles calculation of adsorption of shale gas on CaCO3 (100) surfaces.
To demonstrate the adsorption strength of shale gas to calcium carbonate in shale matrix, the adsorption of shale gas on CaCO3 (100) surfaces was studied using the first-principles method, which is based on the density functional theory (DFT). The structures and electronic properties of CH4, C2H6, CO2 and N2 molecules were calculated by the generalized gradient approximation (GGA), for a coverage of 1 monolayer (ML). Under the same conditions, the density of states (DOS) of CaCO3 (100) surfaces before and after the adsorption of shale gas molecules at high-symmetry adsorption sites were compared. The results showed that the adsorption energies of CH4, C2H6, CO2 and N2 on CaCO3 (100) surfaces were between 0.2683 eV and -0.7388 eV. When a CH4 molecule was adsorbed at a hollow site and its 2 hydrogen atoms were parallel to the long diagonal (H3) on the CaCO3 (100) surface, it had the most stable adsorption, and the adsorption energy was only -0.4160 eV. The change of adsorption energy of CH4 was no more than 0.0535 eV. Compared with the DOS distribution of CH4 before adsorption, it shifted to the left overall after adsorption. At the same time, the partial density of states (PDOS) curves of CaCO3 (100) surfaces before and after adsorption basically overlapped. This work showed that the adsorption effect of shale gas on calcium carbonate is very weak, and the adsorption is physisorption at the molecular level.


Health professionals' perspectives of safety issues in mental health services: A qualitative study.
The study aimed to explore mental health professionals' perceptions of patient safety issues across community and inpatient mental health services. Fourteen mental health professionals across community and inpatient settings participated in qualitative interviews. Framework analysis, guided by the Yorkshire Contributory Factors Framework - Mental Health, was used to analyse the data. Safety issues identified by mental health professionals mapped on to 19 of the 21 factors in the Yorkshire Contributory Factors Framework - Mental Health. The factors most frequently mentioned by participants were 'safety culture' which focused on raising concerns, learning from incidents and the influence of targets; 'communication systems' to support effective communication between staff; 'service user factors' including a perceived increase in illness acuity; 'service process' including how patients access and interact with services; and 'staff workload' perceived being as unmanageable. Mental health professionals consider there to be a broad range of safety issues associated with mental health services. Future research should aim to develop interventions to improve safety focused across the factors raised by professionals.


Rapid increases in the membrane expression of neutral endopeptidase (CD10), aminopeptidase N (CD13), tyrosine phosphatase (CD45), and Fc gamma-RIII (CD16) upon stimulation of human peripheral leukocytes with human C5a.
Rapid increases in the membrane expression of C3 receptors on granulocytes and monocytes in response to the anaphylatoxin C5a have previously been described. In this study we demonstrate increases in the membrane expression of neutral endopeptidase (NEP, CD10, CALLA), aminopeptidase N (APN, CD13), tyrosine phosphatase (CD45/CD45Ro) and the Fc R Fc gamma-RIII (CD16) on granulocytes within minutes of treatment with human C5a. Monocytes responded to C5a with increases in CD13 and CD45/CD45Ro. These membrane modulations could be prevented by preincubating the C5a preparations with anti-C5a mAb C17/5 but not by pretreating the cells with cycloheximide. Increases of CD10, CD13, and CD11b but not CD11a (LFA-1) were also observed in leukocytes from patients undergoing hemodialysis with cuprophan membranes. The increase of CD16 on granulocytes was dependent on the presence of plasma during in vitro activation with C5a indicating that plasma contains inhibitors which prevent the previously described loss of Fc gamma-RIII upon stimulation of the cells.


Surface premelting and melting of colloidal glasses.
The nature of liquid-to-glass transition is a major puzzle in science. A similar challenge exists in glass-to-liquid transition, i.e., glass melting, especially for the poorly investigated surface effects. Here, we assemble colloidal glasses by vapor deposition and melt them by tuning particle attractions. The structural and dynamic parameters saturate at different depths, which define a surface liquid layer and an intermediate glassy layer. The power-law growth of both layers and melting front behaviors at different heating rates are similar to crystal premelting and melting, suggesting that premelting and melting can be generalized to amorphous solids. The measured single-particle kinetics reveal various features and confirm theoretical predictions for glass surface layer.


Arginine ethylester prevents thermal inactivation and aggregation of lysozyme.
Arginine is a versatile additive to prevent protein aggregation. This paper shows that arginine ethylester (ArgEE) prevents heat-induced inactivation and aggregation of hen egg lysozyme more effectively than arginine or guanidine. The addition of ArgEE decreased the melting temperature of lysozyme. This data could be interpreted in terms of ArgEE binding to unfolded lysozyme, possibly through the ethylated carboxyl group, which leads to effective prevention of intermolecular interaction among aggregation-prone molecules. The data suggest that ArgEE could be used as an additive to prevent inactivation and aggregation of heat-labile proteins.


Measuring fluctuating dynamics of sparsely crosslinked actin gels with dual-feedback nonlinear microrheology.
We investigate the fluctuating dynamics of colloidal particles in weakly crosslinked F-actin networks with optical-trap-based microrheology. Using the dual-feedback technology, embedded colloidal particles were stably forced beyond the linear regime in a manner that does not suppress spontaneous fluctuations of particles. Upon forcing, a particle that was stably confined in a cage made of the network's crosslinks started to intermittently jump to the next caging microenvironments. By investigating the statistics of the jump dynamics, we discuss how heterogeneous relaxations observed in equilibrium systems became homogeneous when similar jumps were activated under constant forcing beyond the linear regime.


How to Prevent and Manage Postoperative Complications in Maxillary Sinus Augmentation Using the Lateral Approach: A Review.
Maxillary sinus augmentation with a lateral approach is known to present more postoperative complications than other atrophic posterior maxilla treatment modalities because it is more invasive. These complications include infections that occur in the form of chronic or acute sinusitis. According to the literature, the frequency of these complications ranges from 3% to 5%. They can result from an inadequate management of intraoperative complications or from a poor evaluation of maxillary sinus particularities and pathology before the surgery. Therefore, the prevention of postoperative complications lies in the selection of cases that will allow for the identification and evaluation of infectious risk. Only a multidisciplinary approach that includes an implantologist, a rhinologist, and the treating physician will allow this. On the other hand, in infectious complication cases, the intervention of the otorhinolaryngologist (ENT) specialist is necessary. Based on the available literature and the author's experience, the methodology described in this article will allow for the prevention and management of postoperative complications related to this surgical technique.


Stay-At-Home Orders Are Associated With Emergence of Novel SARS-CoV-2 Variants.
Background While public health strategies to contain the current coronavirus disease 2019 (COVID-19) pandemic are primarily focused on social distancing and isolation, emerging evidence suggest that in some regions social isolation failed to lead to further decrease in the number of COVID-19 deaths in the long run. This apparent paradox was particularly observed in the northern region of Brazil, in the state of Amazonas. We hypothesized that the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, leading to more transmissible and pathogenic variants, could explain the lack of further reductions in COVID-19 new cases and related deaths in some regions. Our objective is to determine if social isolation is associated with the emergence of new SARS-CoV-2 variants, particularly the P.1 lineage and E484K mutants, in Brazil and in the state of Amazonas. Materials and methods We assessed the prevailing SARS-CoV-2 genomes present in Brazil available on the GISAID (Global Initiative on Sharing All Influenza Data) database collected between June 1, 2020, and January 31, 2021. Data regarding demographics, lineage, and prevalence of P.1 lineage and E484K mutations were obtained. Social isolation was measured using the Social Isolation Index (SII), which quantifies the percentage of individuals that stayed within a distance of 450 meters from their homes on a given day, between February 1, 2020, and January 24, 2021. The number of daily COVID-19 deaths was obtained from the Brazilian Ministry of Health (OpenDataSUS, 2021) between March 12, 2020, and January 10, 2021. SII was correlated with the prevalence P.1 lineage and E484K mutations in the eight following weeks. All univariate associations were estimated using the Spearman Correlation Index. 3D surfaces were employed to reflect the relationship between time, social isolation, and prevalence of genomic variants simultaneously. Results A total of 773 and 77 samples were obtained in Brazil and in the Amazonas state, respectively. In the state of Amazonas, SII on a given week was positively, significantly, and moderately or strongly (r > 0.6) correlated with the prevalence of both P.1 lineage and other E484K variants in the six following weeks after the SII on a given week. Conversely, in overall Brazil, correlations between SII and P.1 lineage and E484K variants were weaker and shorter, or negative, respectively. When SII was below 40%, P.1 lineage or E484K variants were not detected in the following weeks. When SII was above 40%, apparently exponential positive correlations between SII and prevalence of both P.1 lineage and E484K variants were observed. Conclusion The results of this study indicate that SII above 40% is associated with the emergence of SARS-CoV-2 E484K variants and P.1 lineage in the state of Amazonas, which was not observed in overall Brazil.


Extended field-of-view in a lensless endoscope using an aperiodic multicore fiber.
We investigate lensless endoscopy using coherent beam combining and aperiodic multicore fibers (MCF). We show that diffracted orders, inherent to MCF with periodically arranged cores, dramatically reduce the field-of-view (FoV), and that randomness in MCF core positions can increase the FoV up to the diffraction limit set by a single fiber core, while maintaining a MCF experimental feasibility. We demonstrate experimentally pixelation-free lensless endoscopy imaging over a 120 μm FoV with an aperiodic MCF designed with widely spaced cores. We show that this system is suitable to perform beam scanning imaging by simply applying a tilt to the proximal wavefront.


A modified chronic infection model for testing treatment of Staphylococcus aureus biofilms on implants.
Bacterial biofilms causing implant-associated osteomyelitis is a severe complication with limited antimicrobial therapy options. We designed an animal model, in which implant associated osteomyelitis arise from a Staphylococcus aureus biofilm on a tibia implant. Two bioluminescently engineered (luxA-E transformed), strains of S. aureus were utilized, Xen29 and Xen31. Biofilm formation was assessed with epifluorescence microscopy. Quantitative measurements were performed day 4, 6, 8, 11 and 15 post-surgery. Bacteria were extracted from the biofilm by sonication and the bacterial load quantified by culturing. Biofilm formation was evident from day 6 post-implantation. Mean bacterial load from implants was ∼1×10(4) CFU/implant, while mean bacterial load from infected tibias were 1×10(6) CFU/bone. Bioluminesence imaging revealed decreasing activity throughout the 15-day observation period, with signal intensity for both strains reaching that of the negative control by day 15 while there was no significant reduction in bacterial load. The model is suitable for testing antimicrobial treatment options for implant associated OM, as treatment efficacy on both biofilm and viable counts can be assessed.


Oral Nitrate Increases Microvascular Reactivity and the Number of Visible Perfused Microvessels in Healthy Volunteers.
Nitric oxide (NO) plays an important role in controlling microcirculatory function, but the effects of exogenous administration of nitrate (NO3-) on the microcirculation have not been well studied. We evaluated whether NO3- could influence the microvascular response to hypoxia in 17 healthy volunteers. We used a vascular occlusion test (VOT) to assess the response of near-infrared spectroscopy-derived indexes to hypoxic stress before and 2 h 15 min after oral administration of 800 mg potassium nitrate. We also monitored changes in the sublingual microcirculation using side-stream dark-field (SDF) video microscopy. The descending (7.3 [6.8-8.1] to 8.2 [7.9-9.8] %/min, p = 0.01) and ascending (201 [180-233] to 240 [197-285] %/min, p = 0.01) thenar oxygen saturation (StO2) slopes were significantly greater during VOT after nitrate administration than before. Sublingual SDF measurements showed increases in the total number of visible perfused vessels (i.e., from 14.1 [13.2-15.5] to 16.3 [15.4-16.7] vessels/mm, p < 0.01) and in the number of visible perfused small vessels (i.e., from 12.2 [11.5-13.7] to 14.2 [13.5-15.3] vessels/mm, p < 0.01) after nitrate administration but no changes in the microvascular flow index or in the proportion of visible perfused vessels, which were already maximal at baseline. Oral administration of nitrate therefore significantly influenced the response to a hypoxic challenge, increasing the number of visible perfused vessels and thus possibly limiting the O2 diffusion distance.


Crimes of the past: defensive temporal distancing in the face of past in-group wrongdoing.
Relegating past in-group transgressions to ancient history might deflect threat to collective identity. Germans (but not Canadians) judged the Holocaust to be more subjectively remote in time when they read only about German-perpetrated atrocities than when this threat was mitigated. Greater subjective distance predicted lower collective guilt, which, in turn, predicted less willingness to make amends (Study 1). Distancing under threat was more pronounced among defensive Germans who felt unjustly blamed by other nations (Study 2). In Study 3, the authors examined the causal role of subjective time. Nondefensive Germans induced to view the Holocaust as closer reported more collective guilt and willingness to compensate. In contrast, defensive Germans reported less collective guilt after the closeness induction. Taken together, the studies demonstrate that how past wrongs are psychologically situated in time can play a powerful role in people's present-day reactions to them.


[Antibacterial activity and mechanism of baicalein].
Baicalein (BAI) is an effective bactericide. The antibacterial activity and mechanism experiments were carried out by determining conductivity and content of macromolecules of membrane penetrability, the oxidative respiratory metabolism and protein synthesis changes and the inhibition of DNA topoisomerase activities. Electrical conductivity and the number of large molecules of BAI increased 2.48% and 1.8%, respectively, than that of the control. However, the membrane integrity did not destroyed by BAI directly. With BAI treatment, inhibition rates of activities for SDH and MDH were 56.2% and 57.4%, respectively, demonstrating that BAI could inhibit cell respiratory. After treated with BAI for 20 h, the total soluble content of proteins decreased by 42.83%. Moreover, the activities of DNA topoisomerase I and II were inhibited completely by 0.2 mmol x L(-1) BAI. These results indicated that BAI had obvious antibacterial activity on Staphylococcus aureus. The mechanism is that it could affect bacterial membrane penetrability, inhibit protein synthesis and influence SDH, MDH and DNA topoisomerase I and II activities to exert its antibacterial functions.


The effects of an occupation-centered cognitive rehabilitation program on elderly individuals with mild cognitive impairment.
[Purpose] This study investigated the effects of an occupation-centered cognitive rehabilitation program on the cognitive function, electroencephalogram amplitude, and daily activity performance of patients with mild cognitive impairment living in a local community. [Subjects and Methods] The subjects were 6 patients (all female; age: 72.5 ± 6.6 years) with mild cognitive impairment. The patients took part in 10 60-minute sessions, over 10 weeks. [Results] The cognitive function scale scores increased, but the increase was not statistically significant. Daily activity performance improved significantly as evidenced by the Instrumental activities of daily living score in Korean Activity Card Sort. Additionally, electroencephalogram SensoriMotorRhythm wave amplitude increased significantly. [Conclusion] The effects of the occupation-centered cognitive rehabilitation program helped increase concentration and daily activity performance.


More Than Just the Target: Blood Pressure, Stroke, and Vascular Cognitive Impairment.
Despite effective treatments, hypertension remains a leading risk factor of any stroke, stroke recurrence, and vascular cognitive impairment. Hypertension is underdiagnosed and undertreated, both in the primary and secondary prevention setting. The current issue of Stroke includes a Focused Update series of 6 review articles covering differing aspects of hypertension and cerebrovascular disease. Traditionally, the goal of antihypertensive treatment has been risk reduction through reaching defined targets, a "one-size-fits-all" approach, both in the acute stroke and in secondary prevention. In this series, there is a shift toward a more individualized approach to blood pressure management in patients suffering from stroke or vascular cognitive impairment, taking several factors in addition to a defined target into account.


A randomized controlled trial for evaluation of lower abdominal laparoscopic cholecystectomy.
To improve minimally invasive outcomes, we designed a new procedure, lower abdominal laparoscopic cholecystectomy (LALC). This study was conducted to evaluate the effects of LALC versus classical (CLC) and single-incision (SILC) laparoscopic cholecystectomy on reducing systemic acute inflammatory response, improving cosmesis, and postoperative pain relief. Beginning from July 2014, 105 patients meeting the inclusion criteria were randomly assigned to three groups: LALC, CLC, and SILC. The primary endpoint was the determination of systemic inflammatory response to the surgery. Other outcome measures included cosmesis, postoperative pain, and perioperative indices. Each of the three groups consisted of 35 patients. The duration of the operation was significantly longer in the SILC group (p= .005). The rates of adverse events were similar. Changes in interleukin-6 (p = .001) and tumor-necrosis factor-α (p = .016) measured before and after surgery differed significantly; patients who underwent LALC had the smallest change in inflammatory response. Cosmesis scores at one (p = .002) and 12 (p = .004) weeks after surgery favored LALC and SILC. Significant differences in pain scores at four (p = .011) and 12 h (p = .024) postoperatively were also observed. In selected patients, LALC shows more advantages in terms of lower systemic inflammatory response, improved cosmesis, and a favorable postoperative pain profile when compared with CLC and SILC.


The retail market for fresh cassava root tubers in the European Union (EU): the case of Copenhagen, Denmark--a chemical food safety issue?
A number of retail shops in Copenhagen sell fresh cassava roots. Cassava roots contain the toxic cyanogenic glucoside linamarin. A survey was made of the shop characteristics, origin of the roots, buyers, shop owner's knowledge of toxicity levels, and actual toxicity levels. Shops selling fresh cassava were shown mostly to be owned by persons originating in the Middle East or Afghanistan, buyers were found to predominantly be of African origin, and sellers' knowledge concerning the potential toxicity was found to be very restricted. Seventy-six per cent of the roots purchased had a total cyanogenic potentials (CNp) above the 50 mg HCN equivalents kg(-1) dry weight (d.w.) proposed as acceptable by an EU working group. Two of 25 roots purchased had CNp higher than 340 mg HCN eq. kg(-1) d.w. The EU has previously made risk assessments concerning cassava and cyanogenic compounds. In the light of the conclusions drawn, the EU needs to make decisions about how to deal with the regulation and control of fresh cassava roots imported to the European food market. Also cassava root products and cassava leaves should be considered.


Nutrition and health (1948) of Aborigines in settlements in Arnhem Land, northern Australia.
During the American-Australian Scientific Expedition to Arnhem Land in 1948, a nutritionist (Margaret McArthur), a medical officer (Brian Billington), a biochemist (Kelvin Hodges) and also the 'flying dentist' (John Moody) observed the nutrition and health of Aborigines in the settlements on Groote Eylandt, at Yirrkala and at Oenpelli, Northern Territory. The results of their research were published in the Records of the American-Australian Scientific Expedition to Arnhem Land Volume 2 Anthropology and Nutrition. (Melbourne University Press, 1960). Although seasonal and regional variations in food supply were a constant problem for nomadic Aborigines living on 'bush tucker' gathered from marine, freshwater and terrestrial ecosystems, the variety of food provided a well-balanced diet according to the international recommendations of 1948. In contrast, improvements in the 1948 diet of Aborigines in the settlements were strongly recommended. 1 An increase in the quantity of food given to older children and adolescents. 2 Regular distribution of fresh fruit and vegetables throughout the year from settlement gardens. 3 Regular supplies of fish, meat and other animal products, particularly for children, adolescents, pregnant and lactating mothers. 4 Increased production of milk and greater care in its handling. 5 Greater use of whole grain cereals in preference to refined products.


Multiple application of drugs in rats--a new port system.
The implantation of a small port system for repeated intravenous applications of drugs in rats is described. The system basically consists of a Teflon catheter which is inserted into the right internal jugular vein. The open end of the catheter under the right foreleg is subcutaneously carried through to the back and closed by a small port. The port then is implanted into a skin pocket on the back of the rat. The advantage of this method is that repeated intravenous injections of drugs into rats can easily be applied with high accuracy. Complications were rarely observed (7%) and could be mastered successfully in all cases.


Ultrastructure of the digestive system of adult Sanguinicola inermis.
The alimentary tract of adult Sanguinicola inermis Plehn, 1905 (Digenea: Sanguinicolidae) was studied by transmission electron microscopy. A highly developed muscular region, likely to be a modified sucker, is present anteriorly to the oesophagus. The tegumental oesophagus, on the basis of the characteristics of the surface cytoplasm, is differentiated into anterior, median and posterior regions with the apical cytoplasm of the median oesophagus drawn into extracellular vesicles from which arise surface knobs. The oesophagus leads to a cellular intestine composed of a single layer of epithelial cells. The apical surface of the intestine is drawn into short luminal projections and the intestinal cells contain numerous organelles and secretory granules. No host cells or cell debris were evident within the alimentary tract, although the intestinal lumen was filled with electron-dense material.


Cloning and expression analysis of a new anther-specific gene CaMF4 in Capsicum annuum.
Our previous study on the genic male sterile-fertile line 114AB of Capsicum annuum indicated a diversity of differentially expressed cDNA fragments in fertile and sterile lines. In this study, a transcript-derived fragment (TDF), male fertile 4 (CaMF4) was chosen for further investigation to observe that this specific fragment accumulates in the flower buds of the fertile line. The full genomic DNA sequence of CaMF4 was 894 bp in length, containing two exons and one intron, and the complete coding sequence encoded a putative 11.53 kDa protein of 109 amino acids. The derived protein of CaMF4 shared similarity with the members of PGPS/D3 protein family. The expression of CaMF4 was detected in both the flower buds at stage 8 and open flowers of the male fertile line. In contrast to this observation, expression of CaMF4 was not detected in any organs of the male sterile line. Further analysis revealed that CaMF4 was expressed particularly in anthers of the fertile line. Our results suggest that CaMF4 is an anther-specific gene and might be indispensable for anther or pollen development in C. annuum.


Onset of sidebranching in directional solidification.
We use a computationally efficient phase-field formulation [B. Echebarria, Phys. Rev. E 70, 061604 (2004)] to investigate the origin and dynamics of sidebranching in directional solidification for realistic parameters of a dilute alloy previously studied experimentally [M. Gorgelin and A. Pocheau, Phys. Rev. E 57, 3189 (1998)]. Sidebranching is found to result either from noise amplification or from deterministic oscillations that exist both in two dimensions and in a three-dimensional thin-sample geometry. The oscillatory branch of growth solutions bifurcates subcritically from the main steady-state branch of solutions and exists over a finite range of large array spacings. In contrast, noise-induced sidebranching is associated with a smooth transition where the sidebranching amplitude increases exponentially with spacing up to nonlinear saturation due to the overlap of diffusion fields from neighboring cells, as observed experimentally. In the latter case where sidebranching is noise-induced, we find that increasing the externally imposed thermal gradient reduces the onset velocity and wavelength of sidebranching, as also observed experimentally. We show that this counterintuitive effect is due to tip blunting with increasing thermal gradient that promotes noise amplification in the tip region.


Individual differences in adult ego development: sources of influence in twins reared apart.
A behavior genetic analysis of the personality dimension of ego development, as assessed by the Washington University Sentence Completion Test, was carried out on a sample of 45 pairs of monozygotic twins and 28 pairs of same-sex dizygotic twins. The twins ranged in age from 16 to 70 years at the time of assessment, had been separated during infancy, and had been raised apart in adoptive homes before being reunited in adulthood. Analyses indicated that reared-apart twins were similar in trait levels of ego development and that such similarity could not solely be attributed to measured similarity in cognitive ability, including verbal reasoning. Estimates of broad similarity for ego development (46%) were comparable to values reported for other major personality dimensions. Phenotypic variance in adult levels of ego development appears to have substantial genetic and environmental sources.


Emotion regulation and posttraumatic stress symptoms: a meta-analysis.
Emotion regulation (ER) has been identified as a critical factor in the development and maintenance of posttraumatic stress symptoms (PTS; Bardeen, Kumpula, & Orcutt, 2013 [Journal of Anxiety Disorders, 27, 188-196]; Marx & Sloan, 2005 [Behaviour Research and Therapy, 43, 569-583]; Nightingale & Williams, 2000 [British Journal of Clinical Psychology, 39, 243-254]). The current meta-analysis aimed to provide a thorough, quantitative examination of the associations between PTS and several aspects of ER. A search of the PsychINFO database resulted in 2557 titles, of which 57 met full inclusion criteria (the cross-sectional association between PTS symptoms and ER was reported, participants were 18 years or older, the article was written in English, and sufficient information was reported to calculate effect sizes). From the 57 studies that were included, 74 effect sizes were obtained. All studies were independently coded by two of the study authors for the following: citation, sample type, total N size (and group n's if applicable), mean age of participants, type of traumatic event, study design, PTS measure(s), ER measure(s), and effect size information. Eight random effects models were conducted: seven for individual ER strategies (e.g., rumination) and one for general emotion dysregulation. The largest effects were observed for general emotion dysregulation (r = 0.53; k = 13), rumination (r = 0.51; k = 5), thought suppression (r = 0.47; k = 13), and experiential avoidance (r = 0.40; k = 20). Medium effects were observed for expressive suppression (r = 0.29; k = 3) and worry (r = 0.28; k = 6). Significant effects were not observed for acceptance or reappraisal. Moderator analyses (sample and trauma type) were conducted for general emotion dysregulation, experiential avoidance, and thought suppression; no significant differences were observed. Findings from the current analysis suggest that several aspects of ER are associated with PTS symptoms across a variety of samples. Additionally, the current study highlights a number of limitations in the existing ER and PTS symptom literature.


ProteinChip array profiling for identification of disease- and chemotherapy-associated biomarkers of nasopharyngeal carcinoma.
We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients. We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters. We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interalpha-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4. Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.


Global analysis of lysine acetylation in strawberry leaves.
Protein lysine acetylation is a reversible and dynamic post-translational modification. It plays an important role in regulating diverse cellular processes including chromatin dynamic, metabolic pathways, and transcription in both prokaryotes and eukaryotes. Although studies of lysine acetylome in plants have been reported, the throughput was not high enough, hindering the deep understanding of lysine acetylation in plant physiology and pathology. In this study, taking advantages of anti-acetyllysine-based enrichment and high-sensitive-mass spectrometer, we applied an integrated proteomic approach to comprehensively investigate lysine acetylome in strawberry. In total, we identified 1392 acetylation sites in 684 proteins, representing the largest dataset of acetylome in plants to date. To reveal the functional impacts of lysine acetylation in strawberry, intensive bioinformatic analysis was performed. The results significantly expanded our current understanding of plant acetylome and demonstrated that lysine acetylation is involved in multiple cellular metabolism and cellular processes. More interestingly, nearly 50% of all acetylated proteins identified in this work were localized in chloroplast and the vital role of lysine acetylation in photosynthesis was also revealed. Taken together, this study not only established the most extensive lysine acetylome in plants to date, but also systematically suggests the significant and unique roles of lysine acetylation in plants.


The role of endogenous antiradical protective system in multiple sclerosis.
Present research aimed at investigation of the role of several inflammatory cytokines and free toxic radicals in Multiple Sclerosis (MS) course and disability progression as well as factors that can assist to the early transition of Relapse Remitting MS (RRMS) in Secondary Progressive MS (SPMS). Totally 22 MS patients, 14 RRMS and 8 SMPS have been investigated. Age at disease onset, disease duration, number of relapses and the Kurtzke Expanded Disability Status Scale (EDSS) scores were collected. Control comprised 10 healthy volunteers matched for age and sex. Brain was visualized by Magnetic Resonance Tomography (MRT- Siemens AVANTO-1.5-Tesla). Blood pro-inflammatory cytokines were detected by Enzyme Linked immunosorbent Assay (ELISA). Blood free toxic radicals and antioxidant enzymes were detected by Electron Paramagnetic Resonance Method (EPR). Statistics was performed using the SPSS-11.0. Blood pro- and anti-inflammatory factors (γ-Interferon, IL-6, IL-10) were elevated in MS patients against control. Increased blood IL-6 and IL-10 found in RRMS as compared to SPMS, while γ-interferon was higher in SPMS (p<0.000). Blood EPR specters of Lypoperoxiradical (LOO-) and superoxide anion (O2-) were increased in SPMS patients compared to RRMS and control. Blood EPR specters of antioxidant enzymes: superoxidismutase (SOD), catalase (CAT) and Glutathione reductase (GR) found elevated in RRMS against SPMS and control. Positive correlation was found between γ-interferon and EDSS (r=+0.52 p<0.05) in SPMS and negative correlation established between SOD and CAT and EDSS (r=-0.84 and r=-0.60 respectively, p<0.05) in RRMS. Multiple logistic regression toward the brain MRI Injury volume proved significance of C reactive protein, γ-interferon and CAT. Present research suggested that the state of endogenous protection system and blood content of antioxidant enzymes (CAT, SOD) in MS patients could play a significant role for early progression of RRMS in SPMS.


Cytologic evaluation of primary and secondary myelodysplastic syndromes in the dog.
Myelodysplastic syndromes are a heterogeneous group of acquired primary and secondary alterations of hematopoietic stem cells that result in cytopenias in blood and cytologic features of dysplasia in blood and/or bone marrow. To better understand the cytologic features that would permit differentiation of primary and secondary forms of myelodysplasia, we reviewed 267 consecutive bone marrow reports from dogs. These reports indicated that 34 dogs (12.7%) had dysgranulopoiesis, dyserythropoiesis, and/or dysthrombopoiesis in >10% of granulopoietic cells, erythroid cells, and/or megakaryocytes, respectively. Thirteen dogs had primary myelodysplastic syndromes, and 21 had secondary myelodysplastic syndromes. Of the 13 dogs with primary myelodysplasia, 4 were subclassified as myelodysplastic syndrome with refractory anemia (MDS-RA), and 9 were subclassified as myelodysplastic syndrome with excess blasts (MDS-EB). Secondary conditions associated with dysplasia in the bone marrow included malignant lymphoma (n = 5), myelofibrosis (n = 3), immune-mediated thrombocytopenia (n = 4), immune-mediated hemolytic anemia (n = 5), multiple myeloma with melphalan administration (n = 1), pyometra with estrogen administration (n = 1), polycythemia vera (n = 1), and thrombopathia (n = 1). MDS-RA was characterized by <5% myeloblasts in bone marrow, normal granulocyte maturation ratio, increased erythroid maturation ratio, and dysplastic changes in >15% of erythroid cells. MSD-EB was characterized by >/=5% myeloblasts in bone marrow, high granulocyte maturation and erythroid maturation ratios, >/=32% dysplastic granulocytes, and the presence of small atypical immature myeloid cells. Secondary myelodysplastic syndromes were characterized by <5% myeloblasts in bone marrow, variable granulocyte maturation and erythroid maturation ratios, and variable dysplastic features. These results indicate that morphology alone cannot be used to distinguish primary and secondary myelodysplastic syndromes in dogs.


Development of UHV dynamic nanostencil for surface patterning.
A dynamic nanostencil system based on a movable atomic force microscopy (AFM) cantilever-borne mask has been developed in ultrahigh vacuum environment. This system is conceived to offer an outstanding nanopatterning capability of nanometer precision as well as in situ AFM characterization with a large scanning range. Evaporation experiments in both static and dynamic mode have been performed successfully on this system, and some crucial technical problems of stencilling technique such as resolution and clogging are investigated. As an important application of molecular electronics, a method to fabricate and connect nanoscale structures with microelectrodes by accurately combining it with static stenciling is presented.


Robotic transaxillary and retroauricular parathyroid surgery.
Current advancement in robotic surgery has provided a safe, precise, 3-dimensional (3D) magnified dissection for parathyroid surgery without the need for CO2 insufflation, and with a better cosmetic outcome due to an invisible scar in the axillary or retroauricular region. Preoperative imaging studies that assist in the localization of lesions have been key elements in patients' selection for targeted parathyroid surgery.


Anisotropic Collective Variables with Machine Learning Potential for Ab Initio Crystallization of Complex Ceramics.
Enhanced sampling molecular dynamics (MD) simulations have been extensively used in the phase transition study of simple crystalline materials, such as aluminum, silica, and ice. However, MD simulation of the crystallization process for complex crystalline materials still faces a formidable challenge due to their multicomponent induced multiphase problem. Here, we realize the ab initio accuracy MD crystallization simulations of complex ceramics by using anisotropic collective variables (CVs) and machine learning (ML) potential. The anisotropic X-ray diffraction intensity CVs provide precise identification of complex crystal structures with detailed crystallography information, while the ML potential makes it feasible to further perform enhanced sampling simulations with ab initio accuracy. We verify the universality and accuracy of this method through complex ceramics with three kinds of representative structures, i.e., Ti3SiC2 for the MAX structure, zircon for the mineral structure, and lead zirconate titanate for the perovskite structure. It demonstrates exceptional efficiency and ab initio quality in achieving crystallization and generating free energy surfaces of all these ceramics, facilitating the analysis and design of complex crystalline materials.


Hereditary angioedema presenting as irritable bowel syndrome: a case of early closure.
Abdominal pain is one of the most common reasons for outpatient and emergency department visits. We present one such case of early closure in a 32-year-old male with recurrent abdominal pain who was diagnosed with irritable bowel syndrome (IBS). Family history was suspicious for hereditary angioedema (HAE). The HAE workup came back positive, and the patient was started on prophylactic therapy, which led to an improvement in symptoms and quality of life. The purpose of this case is to create awareness among physicians to test for HAE in patients diagnosed with IBS who, based on their history or physical examination, have clinical suspicion for HAE.


Is virtual reality effective in improving the motor performance of children with developmental coordination disorder? A systematic review.
Although virtual reality (VR) is an increasingly popular approach within studies that propose interventions for children with developmental coordination disorder (DCD), evidence on the effectiveness of VR remains debatable. The aim of this study was to synthesize evidence on the effectiveness of VR interventions for motor performance improvement in children with DCD. Searches were conducted in the MEDLINE/PubMed, Scopus, Web of Science and ERIC databases to select studies published from 1 January 2006 to 30 November 2017. Two independent reviewers performed the primary study selection based on titles, abstracts and full-text reading; this selection included randomized controlled trials (RCTs) that applied VR interventions to children with DCD and assessed outcomes related to motor performance. The methodological quality of the studies included in the search was assessed through the PEDro scale. PRISMA guidelines and Cochrane recommendations for systematic reviews were followed. The effect size of each intervention was calculated to allow for the interpretation of clinical effects, and the body of evidence was synthesised through the GRADE approach. A total of 2160 publications were retrieved; by the end of the selection process, twelve RCTs had been included. Of these twelve, seven were classified as having high methodological quality. Only three studies satisfied the homogeneity conditions to be assessed through the GRADE system, which showed a low level of evidence in favor of VR for improving the motor performance of children with DCD. Not enough evidence currently exists to support or refute the use of VR over non-VR interventions for improving motor performance in children with DCD. Despite the potential for improving the motor performance of DCD children, the absence of specific protocols prevents formal recommendations of VR for these children. Future studies should consider VR protocols that are more specific regarding the tasks, features and target motor skills to be developed by DCD children. In addition, comparisons of similar groups at baseline, the concealment of allocation and the blinding of assessors are internal validity aspects which deserve researchers' attention.


Does vitamin D level have an effect on COVID-19 positivity and COVID-19 related mortality? A retrospective study.
To explore the possible relationship between vitamin D and coronavirus disease-2019 in an urban population known to have relatively low vitamin D levels. The retrospective study was conducted in Bursa, Turkey, and comprised data of 30 family health centers from March 1 to December 15, 2020, related to diagnosed inpatients of coronovairus disease-2019. The diagnosis was based on polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 infection. Vitamin D levels of these patients were obtained from previous records and compared with those without polymerase chain reaction positivity. Vitamin D levels of positive patients who survived were compared with those who died of coronavirus disease-2019. Data was analysed using SPSS 21. Of the 2,105 patients whose data was retrieved, 212(10%) were positive for coronavirus disease-2019, while 1,893(90%) were negative. Among the positive patients, 89(42%) were men and 123(58%) were women. The overall median age was 45 years (Q1-Q3(Q1: first quartile, Q3: third quartile): 35-56 years). Vitamin D level was not significantly different between the positive and negative patients (p>0.05). Among the positive patients, 2(0.9%) patients did not have new admissions to the designated centers and their data was excluded, 206(97.2%) survived and 4(1.9%) died. There was no significant difference in vitamin D levels between those who survived and those who died (p>0.05). There was no significant relationship found between vitamin D levels and coronavirus disease-2019 infection and related deaths.


Urinary tract infection in randomized phase III studies of canagliflozin, a sodium glucose co-transporter 2 inhibitor.
Canagliflozin, a sodium glucose co-transporter 2 inhibitor, lowers plasma glucose in individuals with hyperglycemia by inhibiting renal glucose reabsorption and increasing glucosuria. Urinary tract infections (UTIs) were characterized in patients with type 2 diabetes mellitus enrolled in Phase III studies of canagliflozin. Analyses were performed in 2 pooled datasets: Population 1 (N = 2313; mean exposure [weeks]: canagliflozin, 24.3; placebo, 23.8) including patients from 4 placebo-controlled studies; Population 2 (N = 9439; mean exposure [weeks]: canagliflozin, 68.1; control, 64.4) including patients from 8 placebo- and active-controlled studies (including patients with renal impairment or high risk of cardiovascular disease, and older patients). Individual studies in special patient populations and 2 active-controlled studies were analyzed separately. Patients with a prior history of UTIs were not excluded from these studies. Urinary tract infection frequency and characteristics were systematically collected, with additional information for each event collected using supplemental electronic case report forms. In Populations 1 and 2, canagliflozin 100 and 300 mg were associated with small increases in the incidence of UTIs compared with control, with no dose-dependence. Urinary tract infections with canagliflozin were similar to those with control in severity, and upper UTIs were infrequent across groups. No increase in serious events or those leading to discontinuation were seen with canagliflozin versus control. Time to the first occurrence of symptomatic UTIs tended to be earlier with canagliflozin than placebo in Population 1, and similar with canagliflozin and control in Population 2; median duration of events was similar across groups in both populations. The proportion of patients with recurrent events was low across groups. Canagliflozin was associated with a small increase in incidence of UTIs in patients with type 2 diabetes mellitus, with no increase in serious or upper UTIs.


Detection of pre-neoplastic and neoplastic prostate disease by MALDI profiling of urine.
The heterogeneous progression to the development of prostate cancer (PCa) has precluded effective early detection screens. Existing prostate cancer screening paradigms have relatively poor specificity for cancer relative to other prostate diseases, commonly benign prostatic hyperplasia (BPH). A method for discrimination of BPH, HGPIN, and PCa urine proteome was developed through testing 407 patient samples using matrix assisted laser desorption-mass spectrometry time of flight (MALDI-TOF). Urine samples were adsorbed to reverse phase resin, washed, and the eluant spotted directly for MALDI-TOF analysis of peptides. The processing resolved over 130 verifiable signals of a mass range of 1000-5000 m/z to suggest 71.2% specificity and 67.4% sensitivity in discriminating PCa vs. BPH. Comparing BPH and HGPIN resulted in 73.6% specificity and 69.2% sensitivity. Comparing PCa and HGPIN resulted in 80.8% specificity and 81.0% sensitivity. The high throughput, low-cost assay method developed is amenable for large patient numbers required for supporting biomarker identification.


Sexual dimorphisms of mRNA and miRNA in human/murine heart disease.
Sexual dimorphisms are well recognized in various cardiac diseases such as ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Thorough understanding of the underlying genetic programs is crucial to optimize treatment strategies specified for each gender. By performing meta-analysis and microarray analysis, we sought to comprehensively characterize the sexual dimorphisms in the healthy and diseased heart at the level of both mRNA and miRNA transcriptome. Existing mRNA microarray data of both mouse and human heart were integrated, identifying dozens/ hundreds of sexually dimorphic genes in healthy heart, ICM, HCM, and DCM. These sexually dimorphic genes overrepresented gene ontologies (GOs) important for cardiac homeostasis. Further, microarray of miRNA, isolated from mouse sham left ventricle (LV) (n = 6 & n = 5 for male & female) and chronic MI LV (n = 19 & n = 19) and from human normal LV (n = 6 & n = 6) and ICM LV (n = 4 & n = 5), was conducted. This revealed that 13 mouse miRNAs are sexually dimorphic in MI and 6 in normal heart. In human, 3 miRNAs were sexually dimorphic in ICM and 15 in normal heart. These data revealed miRNA-mRNA networks that operate in a sexually-biased fashion. mRNA and miRNA transcriptome of normal and disease heart show significant sex differences, which might impact the cardiac homeostasis. Together this study provides the first comprehensive picture of the genome-wide program underlying the heart sexual dimorphisms, laying the foundation for gender specific treatment strategies.


Lipid-Based Vectors for Therapeutic mRNA-Based Anti-Cancer Vaccines.
Cancer vaccines have been widely explored as a key tool for effective cancer immunotherapy. Despite a convincing rationale behind cancer vaccines, extensive past efforts were unsuccessful in mediating significantly relevant anti-tumor activity in clinical studies. One of the major reasons for such poor outcome, among others, is the low immunogenicity of more traditional vaccines, such as peptide-, protein- and DNA- based vaccines. Recently, mRNA emerged as a promising alternative to traditional vaccine strategies due to its high immunogenicity, suitability for large-scale and low-cost production, and superior safety profile. However, the clinical application of mRNA-based anti-cancer vaccines has been limited by their instability and inefficient in vivo delivery. Recent technological advances have now largely overcome these issues and lipid-based vectors have demonstrated encouraging results as mRNA vaccine platforms against several types of cancers. This review intends to provide a detailed overview of lipid-based vectors for the development of therapeutic mRNA-based anti-tumor vaccines.


An estimate of the collective dose to the European population from cardiac X-ray procedures.
There have been significant advances in interventional cardiology in recent years that have resulted in an increase in the frequency of both diagnostic and therapeutic X-ray-guided procedures. The number of coronary angiograms, percutaneous transluminal coronary angioplasties (PTCAs) and coronary stent procedures, as well as pacemaker insertions, has increased across Europe. X-ray-guided procedures are used in the treatment of complex cardiac problems and often involve the use of extended fluoroscopy times and the acquisition of a large number of images. There is increasing concern about the dose levels from these procedures, but their impact on the population dose is less well known. In this paper, the number of coronary procedures in various European countries is estimated and the population dose deduced. In addition, the total collective effective doses for cardiac procedures for various European countries have been estimated. In 2006, the estimated average number of coronary angiograms was 5045 per million population, 1511 per million for PTCAs, 836 per million for stents and 918 per million for pacemaker insertions in the 29 countries studied. The estimated population dose from coronary angiograms, pacemaker insertions, PTCA and stent procedures was 27,000 man Sv.


Improved embryonic stem cell technologies.
Murine embryonic stem (ES) cells have become an indispensable tool for investigating genetic function both in vitro and, importantly, in vivo. Recent advances, including tetraploid aggregation, new site-specific recombinases and RNAi, have enabled more sophisticated manipulation of the ES cell genome. For instance, it is now possible to control gene expression in both a temporally and spatially restricted manner. Such new technologies are answering complex questions surrounding the function and interaction of an increasing number of genes. This chapter will review both the history and recent technological progress that has been made in mouse ES cell derivation, genetic manipulation and the generation of ES cell-derived chimaeric animals.


Efficacy of immune checkpoint inhibitors for in-transit melanoma.
The efficacy of immune checkpoint inhibitors (ICI) in metastatic melanoma is well established. However, there are limited data regarding their efficacy in in-transit melanoma (ITM). This study assessed the efficacy of ICI in patients with ITM. A retrospective review of patients with ITM commenced on an ICI between March 2013 and February 2018 at three tertiary centers in Australia. Patients were excluded if they had previous or synchronous distant metastases. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were based on a composite of radiological and clinical assessments. Fifty-four patients were included: 27 (50%) female; median age 75 (range 26-94); 12 (22%) stage IIIB, 40 (74%) stage IIIC and 2 (4%) stage IIID; 10 (19%) BRAF mutant. Forty (74%) received single-agent anti-PD-1 (pembrolizumab or nivolumab), 8 (15%) single agent anti-CTLA-4 (ipilimumab), 5 (9%) combination anti-PD-1/anti-CTLA-4 (ipilimumab and nivolumab or pembrolizumab) and 1 (2%) combination anti-PD-L1 (atezolizumab) and MEK inhibitor (cobimetinib). The median follow-up was 15 months (2-46).ORR to ICI was 54%: 14 (26%) complete responses; 15 (28%) partial responses; 9 (17%) stable disease; 16 (30%) progressive disease. Thirteen (46%) responders had only one ITM lesion. ORR was 58% for single-agent anti-PD-1, 38% for single-agent anti-CTLA4 and 40% for anti-PD-1/anti-CTLA-4. The median PFS was 11.7 months (6.6-not reached). 1-year and 2-year PFS were 48% and 39%, respectively,. Fourteen progressed locoregionally and 11 progressed distantly. The median OS was not reached. 1-year and 2-year OS were 85% and 63%, respectively. No clinicopathological features were associated with ORR. ICI produce objective responses in ITM and should be considered in patients with unresectable ITM or disease recurrence.


Characterization of new highly selective pyrazolo[4,3-d]pyrimidine inhibitor of CDK7.
Targeting cyclin-dependent kinase 7 (CDK7) provides an interesting therapeutic option in cancer therapy because this kinase participates in regulating the cell cycle and transcription. Here, we describe a new trisubstituted pyrazolo[4,3-d]pyrimidine derivative, LGR6768, that inhibits CDK7 in the nanomolar range and displays favourable selectivity across the CDK family. We determined the structure of fully active CDK2/cyclin A2 in complex with LGR6768 at 2.6 Å resolution using X-ray crystallography, revealing conserved interactions within the active site. Structural analysis and comparison with LGR6768 docked to CDK7 provides an explanation of the observed biochemical selectivity, which is linked to a conformational difference in the biphenyl moiety. In cellular experiments, LGR6768 affected regulation of the cell cycle and transcription by inhibiting the phosphorylation of cell cycle CDKs and the carboxy-terminal domain of RNA polymerase II, respectively. LGR6768 limited the proliferation of several leukaemia cell lines, triggered significant changes in protein and mRNA levels related to CDK7 inhibition and induced apoptosis in dose- and time-dependent experiments. Our work supports previous findings and provides further information for the development of selective CDK7 inhibitors.


The prevalence of osteoporosis among antenatal clinic attendees in a rural mission hospital in South-East Nigeria.
Osteoporosis is a global public health problem characterized by reduction of bone mineral density (BMD). This study aimed to assess the prevalence of osteoporosis among antenatal clinic attendees in a rural Southeastern hospital. This was a cross-sectional study of booking Antenatal Clinic Attendees at Mile 4 Catholic Hospital, Abakaliki, between October 2014 and February 2015. The study participants were selected through systematic random sampling. The BMD of the right calcaneal bone of the participants was measured using the OsteoPro, a Quantitative ultrasound scan. A total of 327 eligible women participated in the study. The average age of the participants was 29 ± 4.5 years. The average parity was 2 ± 1.6 childbirths. The mean T-score was -1.19 ± 4.9. Osteoporosis and osteopenia were recorded in 119 women (36.4%) and 56 women (17.1%), respectively, whereas 152 (46.5%) were within normal range. History of regular exercise by the respondents is statistically significant on the reduction of osteopenia and osteoporosis (P ≤ 0.05). The history of ever use of calcium supplementation by the study participants in the index pregnancy did not have any significant effect on the reduction of osteoporosis. There is a high prevalence of osteoporosis among pregnant women in Southeast Nigeria. This may be due to the predominant poor adherence and low dose of calcium supplementation among pregnant women in this environment. Therefore, there is an urgent need for sensitization on this public health problem.


Abiotrophia defectiva: a rare cause of infective endocarditis.
A case of Abiotrophia defectiva-caused infective endocarditis is described. The patient was successfully treated with penicillin combined with gentamicin. Due to the fastidious nature of the agent, there is a need for special media for isolation and moreover, there is a need for a future development of susceptibility assays applicable to the organism.


Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study.
A fraction of chronic lymphocytic leukaemia (CLL) cases carry highly homologous B-cell receptors (BCR), i.e. characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3), often associated with a restricted selection of IGVK/L light chains. Such 'stereotyped' BCR occur more frequently in CLL with unmutated (UM) than mutated (M) IGHV genes. We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time-to-treatment (TTT) and presence of known prognosticators. Sixty-nine clusters (319 IG-rearrangements, 22.4%) with stereotyped BCR were identified. Among 30 confirmed clusters (>or=3 IG-rearrangements/cluster), we found 14 novel clusters, of which 11 had M IG rearrangements (M clusters) and predominantly (8/11) used IGHV3 subgroup genes. Recurrent cluster-biased amino acid changes were found throughout IGHV sequences of these 'M clusters'. Regarding clinical outcome: (i) UM CLL from the IGHV1-2/1-3/1-18/1-46/7-4-1/IGKV1-39 cluster had poorer prognosis than UM/M cases, or UM cases using the same IGHV genes but not in clusters; (ii) M CLL from the IGHV3-21/IGLV3-21 cluster had TTT similar to UM CLL, and shorter than M CLL expressing IGHV3-21 but not in cluster. Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR.


Antigenic specificity of monoclonal antibodies to human myoglobin.
Two monoclonal antibodies directed against different sites of the human myoglobin molecule have been tested for their cross-reactivities against several myoglobins including seven from mammalian species. The relation between their cross-reactivities and their amino acid sequences had led to a possible localization of two antigenic domains in human myoglobin. Each domain includes residues previously considered not to be directly involved in the antigenic structure of myoglobin. Unlike polyclonal serum antibodies, monoclonal hybridoma antibodies directed to a native protein often fail to bind to supposedly antigenic protein fragments. This is explicable in terms of the concept of antigenic domains. Such domains are numerous and overlapping, each comprising a number of contributory amino acid side chains which need not necessarily include continuous sequences of amino acids and which need not exhibit measurable antigenicity in isolation from the rest of the domain.


Developmental differences in the visual processing of emotionally ambiguous neutral faces based on perceived valence.
The aim of the present research was to assess age-related differences in how children and adults interpret and visually process emotionally ambiguous neutral faces. Children and adults provided neutral child faces with valence and arousal ratings while eye movements were recorded. Consistent with previous research, children and adults both interpreted the neutral faces as negatively valenced. Both age groups showed fewer fixations to the eye region when they rated the faces as positive. However, adults fixated more on the eye region when they rated the faces as negative whereas children fixated more on the eye region when they rated the faces as neutral. This finding may suggest that children strategically allocate attentional resources to the eye region when processing emotionally ambiguous faces to gather critical affective information. These findings have implications for the utilization of neutral faces as an experimental control condition and serve as the foundation for future research on the development of mechanisms that underlie the interpretation of emotionally ambiguous faces.


Song variation of the South Eastern Indian Ocean pygmy blue whale population in the Perth Canyon, Western Australia.
Sea noise collected over 2003 to 2017 from the Perth Canyon, Western Australia was analysed for variation in the South Eastern Indian Ocean pygmy blue whale song structure. The primary song-types were: P3, a three unit phrase (I, II and III) repeated with an inter-song interval (ISI) of 170-194 s; P2, a phrase consisting of only units II & III repeated every 84-96 s; and P1 with a phrase consisting of only unit II repeated every 45-49 s. The different ISI values were approximate multiples of each other within a season. When comparing data from each season, across seasons, the ISI value for each song increased significantly through time (all fits had p << 0.001), at 0.30 s/Year (95%CI 0.217-0.383), 0.8 s/Year (95%CI 0.655-1.025) and 1.73 s/Year (95%CI 1.264-2.196) for the P1, P2 and P3 songs respectively. The proportions of each song-type averaged at 21.5, 24.2 and 56% for P1, P2 and P3 occurrence respectively and these ratios could vary by up to ± 8% (95% CI) amongst years. On some occasions animals changed the P3 ISI to be significantly shorter (120-160 s) or longer (220-280 s). Hybrid song patterns occurred where animals combined multiple phrase types into a repeated song. In recent years whales introduced further complexity by splitting song units. This variability of song-type and proportions implies abundance measure for this whale sub population based on song detection needs to factor in trends in song variability to make data comparable between seasons. Further, such variability in song production by a sub population of pygmy blue whales raises questions as to the stability of the song types that are used to delineate populations. The high level of song variability may be driven by an increasing number of background whale callers creating 'noise' and so forcing animals to alter song in order to 'stand out' amongst the crowd.


CDHPs: as enrollment goes up, a time to tune up.
One of the clearest findings of Mercer's annual National Survey of Employer-Sponsored Health Plans is that more companies are thinking of adopting a consumer-directed health plan (CDHP) approach, and more employees are enrolling in CDHPs at the companies that offer them. The authors discuss the advantages for organizations that offer CDHPs, as well as outline key considerations for companies looking to update, optimize and align their CDHPs with the realities of health care reform. They also explain how CDHPs go hand in hand with wellness and health management strategies, both of which increase collaboration between employees and employers to control costs and give employees more personal responsibility for better outcomes.


CAG Repeats Within the Non-pathological Range in the HTT Gene Influence Personality Traits in Patients With Subjective Cognitive Decline: A 13-Year Follow-Up Study.
HTT is a gene containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. HTT genes with <35 repeats are not associated with HD. The biological function of CAG repeat expansion below the non-pathological threshold is not well understood. In fact higher number of repeats in HTT confer advantageous changes in brain structure and general intelligence, but several studies focused on establishing the association between CAG expansions and susceptibility to psychiatric disturbances and to other neurodegenerative disease than HD. We hypothesized that HTT CAG repeat length below the pathological threshold might influence mood and personality traits in a longitudinal sample of individuals with Subjective Cognitive Decline. We included 54 patients with SCD. All patients underwent an extensive neuropsychological battery at baseline, APOE genotyping and analysis of HTT alleles. We used the Big Five Factors Questionnaire (BFFQ) and Hamilton Depression Rating Scale (HDRS), respectively, to assess personality traits of patients and depression at baseline. Patients who did not progress to Mild Cognitive Impairment (MCI) had at least 5-year follow-up time. In the whole sample, CAG repeat number in the shorter HTT allele was inversely correlated with conscientiousness (Pearson = -0.364, p = 0.007). There was no correlation between HDRS and CAG repeats. During the follow-up, 14 patients [25.93% (95% C.I. = 14.24-37.61)] progressed to MCI (MCI+) and 40 [74.07% (95% C.I. = 62.39-85.76)] did not (MCI-). When we performed the same analysis in the MCI+ group we found that: CAG repeat length on the shorter allele was inversely correlated with energy (Pearson = 0.639, p = 0.014) and conscientiousness (Pearson = -0.695, p = 0.006). CAG repeat length on the longer allele was inversely correlated with conscientiousness (Pearson = -0.901, p < 0.001) and directly correlated with emotional stability (Pearson = 0.639, p = 0.014). These associations were confirmed also by multivariate analysis. We found no correlations between BFFQ parameters and CAG repeats in the MCI- group. Personality traits and CAG repeat length in the intermediate range have been associated with progression of cognitive decline and neuropathological findings consistent with AD. We showed that CAG repeat lengths in the HTT gene within the non-pathological range influence personality traits.


The Need for Biosecurity Education in Biotechnology Curricula.
The growth of biotechnology in recent decades and the dual-use nature of most bioscience research are making their misuse, or accidental misuse or release, more likely and present as threats to biosecurity. A proactive approach is through educating the next generation of scientists to be more security conscious. However, current educational and professional programs in biosecurity are lacking. In this perspective, we recommend that biosecurity educational opportunities should be implemented and expanded for undergraduate and graduate students who will likely use one or more methods in the field of biotechnology. We then propose that biosecurity education is a key factor in a path toward sustainable and safe research. Finally, a set of 17 biosecurity competencies organized into 6 distinct themes is outlined.


[The value of bedside lung ultrasound in emergency-plus protocol for the assessment of lung consolidation and atelectasis in critical patients].
To investigate the effect of the bedside lung ultrasound in emergency(BLUE)-plus lung ultrasound protocol on lung consolidation and atelectasis of critical patients. All patients who need to receive mechanical ventilation for more than 48 hours in ICU from June 2010 to December 2011 in Peking Union Medical College Hospital were included in the study. BLUE-plus and BLUE lung ultrasound, bedside X-ray, lung CT examination were performed on all patients at the same time. The condition of lung consolidation and atelectasis discovered by BLUE-plus lung ultrasound protocol was recorded and compared with bedside X-ray or lung CT. The difference in assessment of lung consolidation and atelectasis between BLUE-plus lung ultrasound protocol and BLUE protocol was compared. A total of 78 patients were finally enrolled in the study. The lung CT found 70 cases (89.74%) had different degrees of lung consolidation and atelectasis. The sensitivity, specificity and diagnostic accuracy of lung consolidation and atelectasis by the bedside chest X-ray were 31.29%, 75.00% and 38.46%, respectively. BLUE-plus lung ultrasound protocol found 68 cases with lung consolidation and atelectasis, and its sensitivity, specificity, and diagnostic accuracy were 95.71%, 87.50% and 94.87%, respectively, which were significantly higher than those of lung CT. BLUE protocol found 48 cases of lung consolidation and atelectasis, and its sensitivity, specificity, and diagnostic accuracy were 65.71%, 75.00% and 66.67%, respectively. The position of lung consolidation and atelectasis which hadn't been found by BLUE protocol was mainly proved to be located in the basement of lung by lung CT. The incidence of lung consolidation and atelectasis in critical patients who received mechanical ventilation is high. The BLUE-plus lung ultrasound protocol has a relatively higher sensitivity, specificity and diagnostic accuracy for consolidation and atelectasis, which can find majority of consolidation and atelectasis. As BLUE-plus lung ultrasound is a bedside noninvasive method allowing immediate assessment of most lung consolidation and atelectasis, it will be likely the alternative of the CT and play a key role in assessment of lung consolidation and atelectasis.


Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. Ciblos Study Group.
Osteoporosis is a well-recognized adverse effect of corticosteroid therapy. This study aimed to investigate the effect of etidronate, intermittent cyclical therapy, in the prevention of corticosteroid-induced bone loss. Patients with various medical conditions starting high-dose corticosteroid therapy were enrolled in the study. The treatment had to be expected to continue for at least 12 months with the initial 90 days at a mean daily dose of at least 7.5 mg of prednisone, with subsequent treatment of at least 2.5 mg/day. One hundred seventeen patients were randomly assigned oral etidronate 400 mg/day, or placebo, for 14 days, followed by 76 days of oral calcium carbonate (500 mg elemental calcium), cycled over 12 months. The primary outcome measure was the difference in percent change from baseline in bone mineral density of the lumbar spine between the groups at the end of year 1. Secondary measures included changes in femur bone density and in biochemical markers of bone remodeling. The mean (+/- SEM) lumbar spine bone density changed 0.30 +/- 0.61% and -2.79 +/- 0.63% in the etidronate and placebo groups, respectively. The mean difference between groups after 1 yr was 3.0 +/- 0.84% (P = 0.004). The changes in the femoral neck and great trochanter were not different between the groups. There was a decrease in pyridinium crosslinks, significant from baseline at both 6 and 12 months, in the etidronate group. Osteocalcin increased in the placebo group, and difference between groups was -25.07 +/- 14.89% (P = 0.032) and -34.68 +/- 19.77% (P = 0.051), at 6 and 12 months respectively. There was no significant difference between the groups in number of adverse experiences, including gastrointestinal disorders. Etidronate intermittent cyclical therapy prevents lumbar vertebral bone loss in patients starting high-dose corticosteroid therapy.


The termination of early pregnancy in the mouse by beta-momorcharin.
beta- Momorcharin is a basic glycoprotein found in the seeds of Momordica charantia L. It differed immunologically from alpha- momorcharin also of the same source but possessed similar mid-term abortifacient activity. Intraperitoneal administration of beta- momocharin into mice on Days 4 and 6 of pregnancy led to an inhibition of pregnancy. In vitro study showed that the protein disturbed peri-implantation development by: (a) blocking the hatching of embryos from the zona pellucida; (b) decreasing the incidence of successful attachment of the blastocyst; (c) reducing the trophoblast outgrowth; and (d) disrupting the development of inner cell mass. It is likely that beta- momorcharin inhibited embryonic implantation by a similar biological action previously described for alpha- momorcharin .


Acquired protein energy malnutrition in glutaric acidemia.
We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica.


Huntingtin Supplies a csaA-Independent Function Essential for EDTA-Resistant Homotypic Cell Adhesion in Dictyostelium discoideum.
The CAG triplet repeat expansion mutation in the HTT locus, which results in neurodegeneration in Huntington's disease, elongates a polyglutamine tract in huntingtin, a HEAT/HEAT-like protein that has been highly structurally conserved through evolution. In several organisms, huntingtin is necessary for proper cell-cell adhesion and normal development. Dictyostelium discoideum huntingtin null (htt-) cells display a variety of developmental abnormalities and completely fail to acquire EDTA-resistant homotypic cell adhesion during starvation in suspension culture. Here, we have assessed the hypothesis that htt may be a genetic interactor of csaA, a major regulator of EDTA-resistant homotypic cell adhesion in D. discoideum. Immunoblot analysis demonstrated that csaA protein expression is dysregulated in htt- cells. Unexpectedly, csaA overexpression, previously shown to rescue csaA- cell adhesion, failed to rescue the htt- adhesion defect. Thus, while htt was required for proper expression of the csaA protein, csaA overexpression was not sufficient to confer EDTA-resistant adhesion in the context of the htt- genetic background in contrast to parental cells. This implies a novel role for htt in conferring csaA-dependent, EDTA-resistant cell adhesion that warrants further investigation. Calcium supplementation restored both endogenous csaA protein levels and EDTA-resistant adhesion in htt- cells. Our data suggests the existence of an additional mechanism that overcomes the EDTA-resistant adhesion defect of htt- cells in the early development of D. discoideum.


Radiology program director's perspective on a novel hands-on advanced elective.
With the advent of the USMLE Step 1 exam moving to a pass/fail status, Radiology Program Directors (PDs) and Associate Program Directors (APDs) need alternative methods of identifying interested and engaged medical students who are applying to their program. Additionally, undergraduate radiology medical education in the United States varies widely from institution to institution with no universal mandatory radiology component. To address these problems, we implemented an advanced fourth year hands-on radiology elective where the students were treated as first year radiology residents (R1s), giving them resident-level access to the Picture Archive and Communication System (PACS) and dictation software, and allowing them to perform entry-level procedures with appropriate supervision. After implementation of the elective, a 5-question online survey was sent to two hundred and ninety-eight PDs and APDs via the Association of Program Directors in Radiology (APDR) listserv, of which seventy-two responses were compiled, yielding a response rate of 24%. The survey focused on how a hands-on medical student elective would help in assessing prospective candidates and predicting R1 performance. Most respondents felt interest in radiology, motivation, and interpersonal skills would be better assessed after such an elective and the vast majority felt hands-on Advanced Elective would be at least slightly predictive of first year resident performance. Based on this information, we believe implementing a hands-on advanced radiology elective would significantly help address the passive nature of traditional radiology electives, providing valuable information to PDs and APDs and giving the best possible radiology experience to our medical students.


Tracheal pressure control provides automatic and variable inspiratory pressure assist to decrease the imposed resistive work of breathing.
To evaluate the operation of a continuous positive airway pressure system by using tracheal airway pressure (PT) as the control signal for system operation (i.e., tracheal pressure control). Repeated measures. University research laboratory. Twelve anesthetized, spontaneously breathing swine. Subjects were intubated and connected to a tracheal pressure control system (5 cm H2O continuous positive airway pressure). Varying inspiratory flow demands and degrees of partial endotracheal tube occlusion (25%, 50%, and 75%) were studied. Tracheal pressure control was compared with a conventionally controlled system (pressure from breathing circuit Y-piece [PY] used as control signal) during endotracheal tube occlusion. Imposed resistive work of breathing (work to spontaneously inhale through endotracheal tube and ventilator circuit), work by ventilation system assisting inhalation, PT, PY, tidal volume, and inspiratory flow demands were measured. As inspiratory flow demands increased (range, 0.2-2.3 L/sec), pressure assist increased automatically (range, 5-40 cm H2O) as well as work of breathing by ventilation system assisting inhalation (range, 0.2-2.5 J/L). Imposed resistive work of breathing was nullified at the lower and was negligible at the higher flow demands. During endotracheal tube occlusion with a conventionally controlled system, PY was unchanged, whereas PT decreased (up to -15 cm H2O) and imposed resistive work of breathing increased (up to 1.05 J/L). With tracheal pressure control, PY increased automatically (range, 8-52 cm H2O), whereas PT varied slightly (range, 2 to -4.6 cm H2O). Imposed resistive work of breathing was negligible (range, 0-0.2 J/L). Breathing circuit pressure (PY), not pulmonary airway pressure (PT), increased significantly during tracheal pressure control. Tracheal pressure control results in automatic and variable levels of pressure assist to decrease imposed resistive work of breathing under conditions of varying spontaneous inspiratory flow demands and endotracheal tube occlusion. Conventional systems are potentially flawed when PY is used as the control signal because they do not function in this manner and do not accurately assess pulmonary airway pressure.


"From Health Experts to Health Guides": Motivational Interviewing Learning Processes and Influencing Factors.
Motivational interviewing is an evidence-based counseling approach. However, its learning processes and their influencing factors are understudied, failing to address the suboptimal use of motivational interviewing in clinical practice. A participatory action research was conducted in collaboration with 16 primary care clinicians, who encountered similar challenges through their previous counseling approaches. The study aimed to facilitate and describe the clinicians' professional transformation through interprofessional communities of practice on motivational interviewing (ICP-MI). Data were collected using the principal investigator's research journal and participant observation of four independent ICP-MIs (76 h) followed by focus groups (8 h). The co-participants performed inductive qualitative data analysis. Results report that learning motivational interviewing requires a paradigm shift from health experts to health guides. The learning processes were initiated by the creation of an openness to the MI spirit and rapidly evolved into iterative processes of MI spirit embodiment and MI skill building. The intrinsic influencing factors involved the clinician's personal traits and professional background; the extrinsic influencing factor was the shared culture disseminating the expert care model. Previously described in a fragmented manner, motivational interviewing learning processes, and its influencing factors were presented as integrated findings. Considerations in elaborating effective MI training/implementation programs are discussed for clinicians, trainers, and decision-makers. Future areas of investigation are also highlighted calling forth the research community to contribute to knowledge advancement on health education in primary care.


Diagnostic delay in a multi-organ tuberculosis immunocompetent patient: a case report.
A 67-year-old immunocompetent male presented with intermittent fever for 3 months associated with urinary incontinence, altered bowel habits and history of loss of appetite and weight. He was treated as having enteric fever at various clinics in the city by different physicians. On evaluation the patient was found to have disseminated tuberculosis with involvement of the lungs, eyes, testes, brain, bone, kidneys, liver, spleen and possibly the gastrointestinal tract. This paper reports a case of disseminated tuberculosis to many organs with significant diagnostic delay more than twelve decades after the discovery of the tuberculosis bacillus by Robert Koch.


SEXUAL SIZE DIMORPHISM AND REPRODUCTIVE INVESTMENT BY FEMALE SPIDERS: A COMPARATIVE ANALYSIS.
We investigate the association between female reproductive investment, absolute size, and sexual size dimorphism in spiders to test the predictions of the fecundity-advantage hypothesis. The relationships between absolute size and sexual size dimorphism and aspects of female reproductive output are examined in comparative analyses using phylogenetically independent contrasts. We provide support for the idea that allometry for sexual dimorphism is the result of variation in female size more so than male size. Regression analyses suggest selection for increased fecundity in females. We argue that fecundity selection provides the only general explanation for the evolution of sexual size dimorphism in spiders.


E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer.
Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.


Maximum likelihood estimation of haplotype effects and haplotype-environment interactions in association studies.
The associations between haplotypes and disease phenotypes offer valuable clues about the genetic determinants of complex diseases. It is highly challenging to make statistical inferences about these associations because of the unknown gametic phase in genotype data. We describe a general likelihood-based approach to inferring haplotype-disease associations in studies of unrelated individuals. We consider all possible phenotypes (including disease indicator, quantitative trait, and potentially censored age at onset of disease) and all commonly used study designs (including cross-sectional, case-control, cohort, nested case-control, and case-cohort). The effects of haplotypes on phenotype are characterized by appropriate regression models, which allow various genetic mechanisms and gene-environment interactions. We present the likelihood functions for all study designs and disease phenotypes under Hardy-Weinberg disequilibrium. The corresponding maximum likelihood estimators are approximately unbiased, normally distributed, and statistically efficient. We provide simple and efficient numerical algorithms to calculate the maximum likelihood estimators and their variances, and implement these algorithms in a freely available computer program. Extensive simulation studies demonstrate that the proposed methods perform well in realistic situations. An application to the Carolina Breast Cancer Study reveals significant haplotype effects and haplotype-smoking interactions in the development of breast cancer.


(-)-salbutamol sulphation in the human liver and duodenal mucosa: interindividual variability.
1. Salbutamol as a beta 2-adrenergic agonist used in the treatment of lung obstructive disease and premature labour. It has a bioavailability of 50% and sulphation is the main route of its metabolism. (-)-Salbutamol retains most of the beta 2-adrenergic activity and, thereby, we describe the interindividual variability in the sulphation rate of (-)-salbutamol in 100 specimens of human liver and duodenal mucosa. 2. The mean rate (pmol/min/mg of salbutamol sulphation was 498 in the duodenum and 141 in the liver with 4-fold variation within +/-2 SD units in both tissues. 3. A modelling approach based on the comparison of the best fittings obtained using a gaussian and the sum of two gaussian curves revealed the presence of two subgroups in the hepatic rate of salbutamol sulphation and their means were 69.5 and 105 pmol/min/mg (p < 0.05). In the duodenum, the rate of salbutamol sulphation approached normality. 4. The rates of salbutamol and 4-nitrophenol sulphation correlated highly (r = 0.853; p < 0.001) in the liver whereas in duodenum the rates of salbutamol and dopamine correlated highly (r = 0.914; p < 0.001), 4-Nitrophenol and dopamine are the diagnostic substrates of phenol- and catechol-sulphotransferases respectively. These findings are consistent with the view that the rate of salbutamol sulphation is higher in the gut than in liver and it varies considerably in both tissues.


Viral and non-viral vectors in gene therapy: technology development and clinical trials.
Gene therapy as part of modern molecular medicine holds great promise for the treatment of both acute and chronic diseases and has the potential to bring a revolutionary era to cancer treatment. Gene therapy has been named the medicine of the future. For the past 10 years various viral and non-viral vectors have been engineered for improved gene and drug delivery. Although various diseases have been targeted, cancer therapy has been addressed to a large extent because of the straight forward approach. Delivery of toxic or immunostimulatory genes by viral and non-viral vectors has been investigated and encouraging results have been obtained in animal models. A large number of clinical trials have been conducted with some highly promising outcome. We propose that combinations of viruses with liposomes or polymers will solve the problem of systemic viral delivery and tumor targeting, bringing a revolution in molecular medicine and in applications of gene therapy in humans.


Characterization of regional differences in resting-state fMRI with a data-driven network model of brain dynamics.
Model-based data analysis of whole-brain dynamics links the observed data to model parameters in a network of neural masses. Recently, studies focused on the role of regional variance of model parameters. Such analyses however necessarily depend on the properties of preselected neural mass model. We introduce a method to infer from the functional data both the neural mass model representing the regional dynamics and the region- and subject-specific parameters while respecting the known network structure. We apply the method to human resting-state fMRI. We find that the underlying dynamics can be described as noisy fluctuations around a single fixed point. The method reliably discovers three regional parameters with clear and distinct role in the dynamics, one of which is strongly correlated with the first principal component of the gene expression spatial map. The present approach opens a novel way to the analysis of resting-state fMRI with possible applications for understanding the brain dynamics during aging or neurodegeneration.